title: Self-aggregated nanoparticles based on amphiphilic poly(lactic acid)-grafted-chitosan copolymer for ocular delivery of amphotericin B.
abstract: BACKGROUND
  The purpose of this study was to develop a self-aggregated nanoparticulate vehicle using an amphiphilic poly(lactic acid)-grafted-chitosan (PLA-g-CS) copolymer and to evaluate its potential for ocular delivery of amphotericin B.
  
  
  METHODS
  A PLA-g-CS copolymer was synthesized via a "protection-graft-deprotection" procedure and its structure was confirmed by Fourier transform infrared spectroscopy, (1)H nuclear magnetic resonance, and X-ray diffraction spectra. Amphotericin B-loaded nanoparticles based on PLA-g-CS (AmB/PLA-g-CS) were prepared by the dialysis method and characterized for particle size, zeta potential, and encapsulation efficiency. Studies of these AmB/PLA-g-CS nanoparticles, including their mucoadhesive strength, drug release properties, antifungal activity, ocular irritation, ocular pharmacokinetics, and corneal penetration were performed in vitro and in vivo.
  
  
  RESULTS
  Fourier transform infrared spectroscopy, (1)H nuclear magnetic resonance, and X-ray diffraction spectra showed that the PLA chains were successfully grafted onto chitosan molecules and that crystallization of chitosan was suppressed. The self-aggregated PLA-g-CS nanoparticles had a core-shell structure with an average particle size of approximately 200 nm and zeta potentials higher than 30 mV. Amphotericin B was incorporated into the hydrophobic core of the nanoparticles with high encapsulation efficiency. Sustained drug release from the nanoparticles was observed in vitro. The ocular irritation study showed no sign of irritation after instillation of the PLA-g-CS nanoparticles into rabbit eyes. The minimal inhibitory concentration of the AmB/PLA-g-CS nanoparticles showed antifungal activity similar to that of free amphotericin B against Candida albicans. The in vivo ocular pharmacokinetic study suggested that the PLA-g-CS nanoparticles have the advantage of prolonging residence time at the ocular surface. The corneal penetration study showed that the PLA-g-CS nanoparticles could penetrate into the cornea.
  
  
  CONCLUSIONS
  Our results suggest that this nanoparticulate vehicle based on a PLA-g-CS copolymer might be a promising system for effective ocular delivery of amphotericin B.
authors.affiliation: Department of Ophthalmology, Yongchuan Hospital, Chongqing Medical University, Chongqing, People's Republic of China.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Zhou
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Wang
authors.forename: Jiuying
authors.initials: J
authors.lastname: Jian
authors.forename: Shengfang
authors.initials: S
authors.lastname: Song
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry*; D060433:Administration, Ophthalmic; D000666:Amphotericin B / Q000008:administration & dosage* / Q000737:chemistry; D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage; D002175:Candida / Q000166:cytology / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000737:chemistry*; D003460:Crystallization / Q000379:methods; D004058:Diffusion; D004339:Drug Compounding / Q000379:methods; D015821:Eye Infections, Fungal / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology; D057927:Hydrophobic and Hydrophilic Interactions; D053769:Nanocapsules / Q000008:administration & dosage* / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D011817:Rabbits
chemical_list: D000180:Acrylic Resins; D000935:Antifungal Agents; D053769:Nanocapsules; C065246:chitosan-poly(acrylic acid); D000666:Amphotericin B; D048271:Chitosan
keywords: amphotericin B; chitosan; nanoparticles; poly(lactic acid)